The objective of the present proposal is to examine the effect of the aging process on several parameters of the humoral immune response in experimental animals. Studies will be directed at establishing the immune status of both T and B cells involved in immunity, tolerance and autoimmunity in mice and rabbits of various ages. Special attention will be given to the cellular events involved in the modulation and maintenance of both acquired and self tolerance. The immune status of B lymphocytes to several self components will be monitored in mice and rabbits of different age groups by using B cell polyclonal activators as probes for B cell competence. A comparison of the immune status of B cells will be made in mice of various ages at the time of tolerance induction and also at intervals after the induction of tolerance in attempts to better understand the changes in the immune status of B cells during the aging process. Other studies will attempt to clarify the cellular mechanisms involved both in the regulation of the immune response and in the changes of such regulation during aging. The results of the above experiments will be applied to our work with autoimmune thyroiditis in an attempt to delineate changes that occur in cells during the aging process and lead to an individual's increased susceptibility to autoimmunity. Related studies will be directed at the examination of the reported resistance of New Zealand mice to the induction of immunological tolerance.